The progression of a normal cell cycle and the transition to subsequent development of transformed cancer cells that exhibit uncontrolled growth, survival and metastasis/angiogenesis involves multiple genetic and epigenetic changes. For most cancers, several critical genes and pathways are responsible for the noted “characteristics” of individual tumors and cancer cells, and development of mechanism-based anticancer agents that target only one gene or pathway have had limited clinical success. In contrast, drug combinations directed to multiple targets in the various pro-oncogenic pathways have been more efficacious.
During the past decade, the discovery of non-coding RNAs (ncRNAs) and the characterization of their functions in both normal and cancer tissues has added to the complexity of cell biology and cell signaling, providing another key element that regulates genes and is associated with, if not influences, cancer cell phenotype. For example, among the different classes of ncRNAs, microRNAs (miRs) have been the most extensively investigated. Functionally, miRs are small ncRNAs (21-23 bp) that exhibit sequence-specific interactions with 3′-UTR sequences in target mRNAs and these interactions generally result in gene repression due to decreased translation and/or mRNA stability. It is estimated that >1000 miRs regulate up to 30% of all protein encoding genes. Several miRs exhibit overexpression that is associated with some different tumors. Functional pro-oncogenic activity of some miRs has been associated with their inhibition of multiple genes with tumor suppressor-like activity.
Despite the advances in the art, there remains a recognized need for improved cancer therapies, including methods of identifying optimal treatments, and methods of monitoring the efficacy of such treatments. Specifically, there is a need to identify additional cancer targets, and drugs that can influence them, to provide additional mechanisms to influence a variety targets in one or more pathways. The invention set forth in this disclosure addresses this need and provides further advantages related thereto.